PROJECT SUMMARY The goal of this competing renewal application is to support the core infrastructure and continued follow-up of the Health Professionals Follow-up Study (HPFS), a cancer epidemiology cohort (CEC) established in 1986 and including 51,529 male health professionals age 40 to 75 years at baseline. This cohort is unique in its focus on men's health and follow-up of almost three decades, a time frame that is essential to realistically understand the relation between modifiable factors and cancer risk. Over this period of time, data has been regularly updated on diet, activity, smoking, weight, medications, and other potentially modifiable determinants of cancer risk. An extensive biorepository has been established that includes DNA from most participants, toenails, red cells, and plasma. Tumor tissue has been obtained from a high percentage of incident prostate and colorectal cancers; a recent supplement is supporting collection of tissue for less common tumors and noncancerous prostate tissue. Cohort follow-up has been consistently 90% or higher at each two-year cycle and mortality follow-up is virtually complete. Epidemiological studies from the HPFS, alone and through participation in consortia, have helped elucidate risk factors for cancer incidence and determinants of cancer survival in men. With cohort members now in an age of high cancer incidence, the HPFS is in a highly productive phase. During the current funding cycle, 325 papers have been published that utilize data and/or biological samples from HPFS; 200 of these have specifically examined cancer or cancer precursor outcomes. To date, 13,346 participants have been diagnosed with cancer and 3,571 cancer deaths have occurred; 5,791 men in HPFS are currently living with a cancer diagnosis. In the next funding cycle, we propose the following aims. 1-) To continue active follow-up for cancer incidence and mortality and to update exposure data pre and post-diagnosis of cancer. 2-) To update the food composition database that supports dietary assessment in HPFS and the Nurses' Health Study I and II cohorts. 3-) To leverage a recently completed validation study of physical activity and collaborate with colleagues in two multiethnic cohorts of men to calibrate physical activity questions. 4-) To make a first time linkage to Medicare Claims data. 5-) To maintain the HPFS cancer tissue biorepository, and expand collections of prostate and colon, and undertake a new collection of lung cancer in nonsmokers. 6-) To maintain the other biorepositories including plasma, red blood cells, germline DNA, and toenail samples. 7-) To undertake a new post-diagnostic blood collection among men with prostate cancer. 8-) To maintain and augment the statistical infrastructure and data management of the cohort. 9-) To facilitate resource sharing and collaborations with other CECs and outside investigators. With additional cohort follow- up, particularly after cancer diagnosis, the HPFS remains ideally positioned to make innovative contributions to our overall goal of reducing the burden of cancer by identifying primary and secondary prevention strategies.